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Andexanet alfa has been found to reverse the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban, according to a study presented at the American Heart Association scientific sessions and published simultaneously in the Nov. 11 issue of the New England Journal of Medicine.
In a two-part randomized, placebo-controlled study involving 145 healthy individuals with a mean age of 58 years, patients treated first with apixaban and then given a bolus of andexanet had a 94% reduction in anti-factor Xa activity, compared with a 21% reduction with placebo. Thrombin generation was restored in 100% of patients within 2-5 minutes.
In the patients treated with rivaroxaban, treatment with andexanet reduced anti-factor Xa activity by 92%, compared with 18% with placebo. Thrombin generation was restored in 96% of participants in the andexanet group, compared with 7% in the placebo group.
Adverse events associated with andexanet were minor, including constipation, feeling hot, or a strange taste in the mouth, and the effects of the andexanet also were sustained over the course of a 2-hour infusion in addition to the bolus (N Engl J Med. 2015 Nov 11. doi: 10.1056/NEJMoa1510991).
“The rapid onset and offset of action of andexanet and the ability to administer it as a bolus or as a bolus plus an infusion may provide flexibility with regard to the restoration of hemostasis when urgent factor Xa inhibitor reversal is required,” Dr. Deborah M. Siegal of McMaster University, Hamilton, Ont., and coauthors wrote.
The study was supported by Portola Pharmaceuticals, Bayer, Bristol-Myers Squibb, Johnson & Johnson, and Pfizer. Several authors are employees of Portola, one with stock options and related patent. Other authors declared grants and personal fees from the pharmaceutical industry, including the study supporters.
Factor Xa inhibitors represent an important advance in anticoagulation therapy, but concern over the lack of antidotes has tempered enthusiasm for their use among patients and physicians. Warfarin is perceived as being safer as a result of the availability of effective reversal strategies.
Although additional studies will be needed to optimize the use of andexanet and to determine its true efficacy and safety, it represents a giant step forward in our ability to control anticoagulation therapy.
Dr. Jean M. Connors is with the hematology division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. These comments are taken from an accompanying editorial (N Engl J Med. 2015 Nov 11. doi: 10.1056/NEJMe1513258). Dr. Connors declared personal fees from Boehringer Ingelheim and Bristol-Myers Squibb outside the submitted work.
Factor Xa inhibitors represent an important advance in anticoagulation therapy, but concern over the lack of antidotes has tempered enthusiasm for their use among patients and physicians. Warfarin is perceived as being safer as a result of the availability of effective reversal strategies.
Although additional studies will be needed to optimize the use of andexanet and to determine its true efficacy and safety, it represents a giant step forward in our ability to control anticoagulation therapy.
Dr. Jean M. Connors is with the hematology division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. These comments are taken from an accompanying editorial (N Engl J Med. 2015 Nov 11. doi: 10.1056/NEJMe1513258). Dr. Connors declared personal fees from Boehringer Ingelheim and Bristol-Myers Squibb outside the submitted work.
Factor Xa inhibitors represent an important advance in anticoagulation therapy, but concern over the lack of antidotes has tempered enthusiasm for their use among patients and physicians. Warfarin is perceived as being safer as a result of the availability of effective reversal strategies.
Although additional studies will be needed to optimize the use of andexanet and to determine its true efficacy and safety, it represents a giant step forward in our ability to control anticoagulation therapy.
Dr. Jean M. Connors is with the hematology division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. These comments are taken from an accompanying editorial (N Engl J Med. 2015 Nov 11. doi: 10.1056/NEJMe1513258). Dr. Connors declared personal fees from Boehringer Ingelheim and Bristol-Myers Squibb outside the submitted work.
Andexanet alfa has been found to reverse the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban, according to a study presented at the American Heart Association scientific sessions and published simultaneously in the Nov. 11 issue of the New England Journal of Medicine.
In a two-part randomized, placebo-controlled study involving 145 healthy individuals with a mean age of 58 years, patients treated first with apixaban and then given a bolus of andexanet had a 94% reduction in anti-factor Xa activity, compared with a 21% reduction with placebo. Thrombin generation was restored in 100% of patients within 2-5 minutes.
In the patients treated with rivaroxaban, treatment with andexanet reduced anti-factor Xa activity by 92%, compared with 18% with placebo. Thrombin generation was restored in 96% of participants in the andexanet group, compared with 7% in the placebo group.
Adverse events associated with andexanet were minor, including constipation, feeling hot, or a strange taste in the mouth, and the effects of the andexanet also were sustained over the course of a 2-hour infusion in addition to the bolus (N Engl J Med. 2015 Nov 11. doi: 10.1056/NEJMoa1510991).
“The rapid onset and offset of action of andexanet and the ability to administer it as a bolus or as a bolus plus an infusion may provide flexibility with regard to the restoration of hemostasis when urgent factor Xa inhibitor reversal is required,” Dr. Deborah M. Siegal of McMaster University, Hamilton, Ont., and coauthors wrote.
The study was supported by Portola Pharmaceuticals, Bayer, Bristol-Myers Squibb, Johnson & Johnson, and Pfizer. Several authors are employees of Portola, one with stock options and related patent. Other authors declared grants and personal fees from the pharmaceutical industry, including the study supporters.
Andexanet alfa has been found to reverse the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban, according to a study presented at the American Heart Association scientific sessions and published simultaneously in the Nov. 11 issue of the New England Journal of Medicine.
In a two-part randomized, placebo-controlled study involving 145 healthy individuals with a mean age of 58 years, patients treated first with apixaban and then given a bolus of andexanet had a 94% reduction in anti-factor Xa activity, compared with a 21% reduction with placebo. Thrombin generation was restored in 100% of patients within 2-5 minutes.
In the patients treated with rivaroxaban, treatment with andexanet reduced anti-factor Xa activity by 92%, compared with 18% with placebo. Thrombin generation was restored in 96% of participants in the andexanet group, compared with 7% in the placebo group.
Adverse events associated with andexanet were minor, including constipation, feeling hot, or a strange taste in the mouth, and the effects of the andexanet also were sustained over the course of a 2-hour infusion in addition to the bolus (N Engl J Med. 2015 Nov 11. doi: 10.1056/NEJMoa1510991).
“The rapid onset and offset of action of andexanet and the ability to administer it as a bolus or as a bolus plus an infusion may provide flexibility with regard to the restoration of hemostasis when urgent factor Xa inhibitor reversal is required,” Dr. Deborah M. Siegal of McMaster University, Hamilton, Ont., and coauthors wrote.
The study was supported by Portola Pharmaceuticals, Bayer, Bristol-Myers Squibb, Johnson & Johnson, and Pfizer. Several authors are employees of Portola, one with stock options and related patent. Other authors declared grants and personal fees from the pharmaceutical industry, including the study supporters.
FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:Andexanet reverses the anticoagulant effects of factor Xa inhibitors rivaroxaban and apixaban in healthy older adults.
Major finding: Andexanet achieved a 92%-94% reduction in anti-factor Xa activity, compared with an 18%-21% reduction with placebo.
Data source: A two-part randomized, placebo-controlled study in 145 healthy individuals.
Disclosures: The study was supported by Portola Pharmaceuticals, Bayer, Bristol-Myers Squibb, Johnson & Johnson, and Pfizer. Several authors are employees of Portola, one with stock options and a related patent. Other authors declared grants and personal fees from the pharmaceutical industry, including the study supporters.